1080 PAQUETTE, WITTENBROOK, AND SCHREIBER spectrum showed absorption a t 6.05 p (carbonyl) and the nmr spectrum exhibited only aromatic proton absorption, a 6 H multiplet a t 6 7.8-8.1 and a 14 H muliplet a t 7.0-7.5. Anal. Calcd for CzoHzoOs: C, 83.65; H, 4.81; mol wt, 416. Found: C, 83.39; H, 4.81; mol wt, 420,415. Reduction of Z-Benzoyl-l,3,5-triphenyl-2-butene-l ,I-dione(9). -A sample of 9 (0.43 g, 0.001 mol) and 0.41 g (0.006 mol) of zinc powder were refluxed in 50 ml of glacial acetic acid for 1 hr. The reaction mixture was added to water and extracted with ether. Acetic acid was removed by extraction with 5% sodium hydroxide solution until the extracts were alkaline. The ethereal solution was washed with water, dried over calcium chloride, and evaporated to yield a residue (0.34 g, 85% yield), mp 168172'. On recrystallization from ethanol, pale yellow crystals (mp 175-176') were obtained that were identified as 1 from mixture melting point and spectral data. Z-Benzoyl-l,3,4-triphenylbutane-1,4-dione(14).Sodium hydride (1.2 g, 0.028 mol), 56% by weight in mineral oil, was washed three times with small quantities of petroleum to remove the mineral oil, and added, under nitrogen, to a flask containing 150 ml of anhydrous 1 ,a-dimethoxyethane. a-Desylacetophenone18 (8.0 g, 0.026 mol) was added and the system was heated a t 55' until the evolution of hydrogen gas had ceased (45 min). Vigorous evolution of gas occurred only near the end of the reaction. Benzoyl chloride, 1.75 g (0.01 mol), in 25 ml of 1,2dimethoxyethane, was added dropwise to the dark-red solution. The reaction mixture was heated for 30 min and poured onto cracked ice. After acidification, the reaction mixture was extracted with ether. The ether solution was extracted with 5% sodium hydroxide solut-ion until the extracts produced no more solid on acidification. The alkaline extracts were combined, acidified, and extracted with ether. The ethereal solution was
The Journal of Organic Chemistry washed with water, dried over calcium chloride, and evaporated to yield 3.07 g (58% yield) of 14, mp 164.5-165' (from ethyl ether), The infrared spectrum showed carbonyl absorption at 5.95 and 6.05 p. The nmr spectrum revealed 1 H (methinyl) doubleb centered a t 6 6.33 and 5.73 (J S 5.1 cps) and a 20 H (aromatic) multiplet at 6.8-8.0. Anal. Calcd for CzoHnOs: C, 83.25; H , 5.26. Found: C, 83.22; H, 5.21. The ether solution remaining after alkaline extraction was washed with water, dried over calcium chloride, and evaporated. Recrystallization of the residue gave 3.95 g (99% recovery) of w-desylacetophenone, mp 124-126' (1it.lg mp 126'). Dehydration of 2-Benzoy1-1,3,4-triphenylbutane-l ,I-dione (14).-A sample of 14 (1.0 g, 0.0024 mol) and 6.0 ml of concentrated hydrochloric acid were refluxed in 200 ml of ethanol for 2.5 hr. After evaporation of solvent, the residue was triturated with ethanol to yield 0.83 g (87% yield) of pale yellow solid, mp 175-176' (from ethanol). On admixture with 1, no depression was observed in the melting point. The infrared spectra of the two samples were identical.
Registry N0.-1,15440-99-0; 2, 13249-75-7; 3, 1381016-7; 4 (R = R' = Ph), 134-81-6; 8, 15441-02-8; 9, 15441-03-9; 14, 15441-04-0; phenoxide ion, 3229-70-7. Acknowledgments.-We are grateful to Dr. M. R. Willcott of the University of Houston for obtaining the nmr spectra. We also acknowledge the assistance of Mr. James Doty and Mr. Tommy Wilbanks who prepared some of the starting materials,
Directive Effects in the Chlorination of Benzyl Chloromethyl Sulfides' LEOA. PAQUETTE,~ LAWRENCE S. WITTENBROOK, AND KARLSCHREIBER~ Department of Chemistry, The Ohio State University, Columbus, Ohio .@$lo Received September 18, 1967
A series of benzyl chloromethyl sulfides has been prepared and treated sequentially with sulfuryl chloride and m-chloroperbenzoic acid. Separation and analysis of the resulting chloro sulfone mixtures have established the much greater directing influence of a chlorine atom when compared with a substituted phenyl group, except when the aromatic ring carries a p-nitro substituent.
When a sulfide possessing at least one hydrogen at an a-carbon atom is treated with 1 equiv of chlorine,4 sulfuryl ~hloride,~Jj or N-chlorosuccinimide (NCS)l t 7 in an inert solvent, a-chloro sulfides are produced. Addition of larger amounts of chlorinating agent generally results in more extensive halogenation.Bai8 A major portion of the interest associated with this reaction derives from the unresolved nature of the detailed mechanism involved in the a-chlorination p r o c e s ~ . ~ * ~ ~ ~ (1) *Halo Sulfones.
Only a limited number of isolated reports have appeared concerning directive effects in the chlorination of sulfides. Thus, chlorination of benzyl alkyl sulfides such as 1l0 and 2 1 1 has been shown to lead only to a-chlorobenzyl sulfides. Chlorinated isomers 4 and 5 are formed in the ratio of 1.6: 1 when benzyl p-chloroCJ45CH2SCH, 1
C&15CHSCH3
I
C1
Paper IX. For previous paper in this series, see
L. A. Paquette and J. C. Phillips, Tetrahedron Lett., 4645 (1967). The authors wish to express their appreciation to the National Science Foundation for funds used in partial support of this Research Fellow, 1965-1967. (2) Alfred P . Sloan Foundation Research Fellow, 1965-1967. (3) Undergraduate research participant, 1965-1966. (4) H. Bohme, H. Fischer, and R. Frank, Ann., 668, 54 (1949), and pertinent references cited therein. (5) (a) F . G . Bordwell and B. M . Pitt, J . Amcr. Chem. Sac., 77, 572 (1955); (b) F. G. Bordwell, G. D. Cooper, and H. Morita, ibid., 79, 376 (1957). (6) (a) W. E. Truce, G . H. Birum, and E. T . McBee, ibid., 74,3594 (1952); (b) L. A. Paquette, ibid., 86, 4085 (1964). (7) (a) D. L. Tuleen and T . B. Stephena, Chern. Ind. (London), 1555 (1968); (b) D. L. Tuleen and V. C. Marcum, J . Org. Chem., 81,204 (1967). (8) (a) L. A. Paquette, J . Amsr. Chem. Sac., 86, 4089 (1964); (b) L. A. Paquette and L. 8.Wittenbrook, ibid., 80, 4483 (1967); (0) L. A. Paquette, L. 8.Wittenhrook, and V. V. Kane, ibid., 89, 4487 (1967); (d) L. 8.Wittenbrook, unpublished observations. (9) C. C. Price and 8.Oae, "Sulfur Bonding," The Ronald Press Co., New York, N. Y., 1962, P 59.
2
5
WSCH2SCH2CQH,CI-p 3
+
7c1
C&I~CH2SCHC~H~Cl-p CeH5 HSCHZCeH4Cl-p
I c1 4
5
benzyl sulfide (3) is treated with an equimolar quantity of N-chlorosuccinimide in carbon tetrachloride solu(10) F. G . Bordwell and G. D. Cooper, J . Amer. Chem. S O C . ,7 3 , 5187 (1951). (11) H. Bohme, L. Tile, and B. Unterhalt, Chem. Ber., 97, 179 (1964).
Vol. 33, No. 3, March 1968
CHLORINATION OF BENZYL CHLOROMETHYL SULFIDES 1081
t i ~ n . ' ~Polychlorination of dimethyl sulfide results in all the hydrogens of one carbon atom being replaced by chlorine before the second methyl group is attacked.6a The same substitution behavior is displayed by chlorosulfides 68cand 7.sd Whereas reaction of dibenzyl CJ&CH2SCH2Cl
C6H5CH,SCHCl2
6
7
sulfide with 2 equiv of sulfuryl chloride produces the a,a-dichloro sulfide as the only product,8a it has been observed that 2,7-dihydro-3,4-5,6-dibenzothiepin (8) interestingly affords a mixture of 9 and 10 in a
when the shielding constant for chlorine is taken into consideration. The electron-impact-induced fragmentations of 12b and 12c were found to result predominantly in direct cleavage of the benzylic C S bond to give the corresponding tropylium cations. Thus, the mass spectrum of 12b displayed a base peak at m/e (C&Cl+) and that of 12c a base peak at m/e 159 (Cd&$"+). No other peaks of greater than 15% relative intensity were observed.l2 In contrast to the above results, when chloromethyl p-nitrobenzyl sulfide (14) was treated with 1 molar equiv of sulfuryl chloride and the crude mixture of dichloro sulfides was oxidized directly with MCPBA, the isomeric dichloro sulfones 15 and 16 were formed in CHZSCH2C1
I
CHClSOzCHzCl
I
CH2SOZCHC12
I
I
NO2 14
8
10
9
ratio of 3.6: 1 (based upon the isolation of pure dichloro sulfones) under the same conditions;s" in the latter case, it has been proposed that the strong inductive effect of the a-chloro substituent in the intermediate a-chloro sulfide is offset by steric factors operative in the transition state for a ,a-dichlorination leading to substitution in the opposite direction. The present study describes directive effects operative in the sulfuryl chloride chlorination of a group of selected benzyl chloromethyl sulfides in which structural modifications have been introduced to provide additional insight into the requirements of such competitive proton abstraction processes and the mechanism of halogenation.
Results and Discussion The sequential reaction of chloromethyl p-fluorobenzyl sulfide (lla) with 1 equiv of sulfuryl chloride and excess m-chloroperbenzoic acid (MCPBA) in chloroform solution afforded a mixture consisting of 12a (80%) and 13a (20%). Chlorination of chloroCH2SO2CHsC1 I
11
J3
12 a,
X = p-F; b,X- p-CI;
c, X = mCF,
methyl p-chlorobenzyl sulfide (1 lb) and chloromethyl m-trifluoromethylbenzyl sulfide (1 IC) under similar conditions produced dichloro sulfones 12b and 12c, respectively, as the only dichlorinated products. No evidence of halogenation at the benzylic methylene group was detected upon close examination of the nmr spectra of the crude reaction mixtures before and after oxidation. The mono- and dichloro sulfones were identified by elemental analysis and by their nmr and mass spectra. The chemical shifts of the various asulfonyl proton absorptions which are collected in Table I are seen to be unexceptional for these six compounds
a ratio of 3 :2. The nmr spectra of 15 and 16 (Table I) are closely related to those of compounds with similar structures. With particular regard to the spectrum of 15,it should be noted that the protons of the methylene TABLE
1
CHEMICAL SHIFTSO F BENZYLIC A N D NONBENZYLIC CX-SULFONYL PROTON( s) IN SELECTED WCHLORINATED SULFONES" 8, ppm
Compd
Benzylic
Nonbenzylic
Dibenzyl sulfone 4.10 CeHsCHzSOzCHClCsHs 4.44 (5.42) 13a 4.41 4.26 13b 4.37 4.21 13c 4.46 4.27 ~ - N O & S H & H ~ S O ~ C H ~ C ~ 4.53 4.32 CsHsCH2SOtCHClz 4.56 6.04 12a 4.51 6.03 12b 4.53 6.06 12c 4.58 6.10 16 4.71 6.22 15 6.13 4 . 5 1 , 5 . lob 18 5.12 17 4.88 CsHbCH2SOzCCls 4.77 4 Spectra were determined on ca. 15% solutions in CDClr; values are reported relative to internal tetramethylsilane and refer to singlets unless otherwise indicated. b AB pattern, J A B = 13 He.
group appear as an AB pair of doublets. The nonequivalency of these protons, presumably caused by the spatial proximity of the asymmetric benzylic carbon atom, has been observed with a limited number of su1f0nes.l~ In further confirmation of the structural assignments, the mass spectrum of 16 was found to exhibit a base peak at m/e 136 (C7HaN02) + as expected from the analogous fragmentation of chloromethyl p-nitrobenzyl sulfone. The mass spectrum of 15 is clearly seen to be that of an a-chloro-p-nitrobenzyl sulfone because of the base peak at m/e 170 (C~HSClNO2 +). (12) T h e favored fragmentation of eulfoneu to give R + and RSOz' has been recognized previously: R. T. Aplin and K . Bailey, J . Chem. Soc., Sect. B, 513 (1987). and appropriate referenow cited therein. (13) J. J. Looker, J . Ow. Chem., 11,2973 (1988);eeealao ref 7b.
1082
Chlorination of 14 with an excess (1.5 molar equiv) of sulfuryl chloride led after oxidation to a mixture of 15 (54%) and the isomeric trichloro sulfones 17 (380/0)and 18 (8%). Assignment of structure to 17 qHZS02CCls
L 1.5 equiv
l4
The Journal of Organic Chemistry
P A Q U E T T E , WITTENBROOK, AND SCHREIBER
2.MCPBA
15
+
(QSOzCHpCl
4 6 4-
I
CHClSCH&l
c)
I
NOz
NO2
17
18
and 18 again rests on their nmr and mass spectra. Whereas 17 produces a base peak at m/e 136 (C?HeNO2+)upon electron impact, trichloro sulfone 18 is seen to undergo extensive fragmentation (base peak m/e 43). The data presented here definitively establish the much greater directing influence of a chlorine atom when compared with a substituted phenyl group, except when the aromatic ring carries a p-nitro substituent. Even in this case, however, a more or less equitable situation obtains (ratio 1.5:1). Although the observed directive effects are inconsistent with the suggestion of Price and Oae9 that the chlorination of sulfides by sulfuryl chloride may proceed by means of an intermediate radical stabilized by octet expansion of the adjacent sulfur atom, they do agree with the intervention of an ionic mechanism. Subsequent to S-chloro-
NO2 19
20
to p-nitrobenzyl trichloromethyl sulfide (isolated as its sulfone). Furthermore, the total absence of trichloro sulfones in the run performed with 1 equiv of sulfuryl chloride points to the fact that the reactivity of the various chloro sulfides toward the chlorinating agent is 14 >> 19 > 20. Since relative rates of chloro sulfonium salt formation very likely represent a quantitative assay of the relative basicities of benzylic sulfides toward the chloronium donor,?b the preceding evidence indicates that the same order holds for the basicities of the chloro sulfides in question. Experimental SectionI4 General Procedure for the Preparation of Mercaptans.-A solution of 9.45 g (0.05 mol) of p-fluorobenzy! bromide and 4.57 g (0.06 mol) of thiourea in 40 ml of 707, aqueous ethanol was refluxed with stirring for 2 hr and cooled. At this point a small aliquot was isolated and the thiuronium bromide was recrystallized from ethanol to purity, mp 144-145'. Anal. Calcd ;or C&HloBrFN2S: C, 36.23; H , 3.80; N , 10.57. Found: C, 36.19; H, 3.96; Y, 10.83. The remainder of the cold solution was added slowly to a saturated aqueous solution of 16.8 g (0.2 mol) of sodium bicarbonate. The precipitated carbonate salt was separated by filtration and the filtrate was neutralized with hydrochloric acid. After the majority of the carbonate salt had been steam distiled, the neutralized filtrate was added and the steam distillation continued. The liberated mercaptan was extracted with ether; the ether solution was dried and evaporated and the residue was distilled to give 6.32 g (89y0) of p-fluorobenzyl mercaptan, bp 69' (6 mm). Anal. Calzd for C7H7FS: C, 59.12; H, 4.96; S, 22.55. Found: C, 59.78; H, 4.88; S,22.59. From m-trifluoromethylbenzyl chloride (Pierce Chemical Co.) there was prepawl the thiuronium chloride, mp 194.5-195.5' (from ethanol) and the mercaptan, bp 55" (2.1-2.2 mm), TP*D 1.4890. Thelatter substance was isolated in 727, yield. Anal. Calcd for CeH&lFsN&: C, 39.93; H, 3.72; N , 10.35. Found: C, 39.94; H, 3.80; N , 10.45. Anal. Calcd for CsHTFsS: C, 49.99; H , 3.67; S, 16.68. Found: C,50.30; H, 3.65; S, 16.94. General Procedure for the Preparation of Benzyl Chloromethyl SuHdes.-Treatment of a solution of 47.6 g (0.30 mol) of pchlorobenzylmercaptan (Wateree Chemical Co.) in 100 ml of dichloromethane with 9.0 g (0.30 mol) of paraformaldehyde and anhydrous hydrogen chloride a t - 20" under the prescribed conditions gave 43.7 g (70.5%) of llb, bp 118-119' (0.4mm). Oxidation of a small portion of this material with m-chloroperbenzoic acid in chloroform solution7 gave 13b, mp 155" (from cyclohexane). Anal. Calcd for CsHSCl2O2S: C, 40.18; H, 3.37. Found: C, 40.29; H, 3.48.
DCH,SCH,C~ + soZci2
X
(within experimental error) is operative in both cases as, of course, it should be. Interestingly, however, dichloro sulfide 19 is converted into its S-chlorosulfonium chloride at a more rapid rate than is dichloro sulfide 20, as indicated by the total conversion of 19
-.c
c1
Cl
1
A
C1
1
sulfonium salt formation, the more acidic a hydrogen is subject to abstraction and the resulting ylide is transformed t o the observed a-chloro sulfide. On this basis, the nature of the products would be expected to be controlled by the relative acidities of the a protons which, in turn, reflect the relative basicities of the substituents (chlorine and substituted phenyl in the present instance) in the transition state. The present work emphasizes the powerful effect of the a-chloro substituent in this regard; only when the phenyl substituent bears a p-nitro substituent can it compete somewhat effectively with this halogen. In conclusion, a further comment relevant to the results obtained when 14 was treated with excess sulfuryl chloride is in order. Comparison of the direction of initial chlorination in this run (ratio of 15 and 18 to 17 = 1.6:l) with the data when only 1 equiv of chlorinating agent was employed (ratio of 15 to 16 = 1.5:l) indicates that the same directional effect
(14) Melting points are corrected and boiling points are uncorrected. The mioroanalyses were performed by the Scandinavian Microanalytical Laboratory, Herlev, Denmark, and by Galbraith Laboratories, Inc., Knoxville, Tennessee. Infrared spectra were determined with a Perkin-Elmer Model 237 spectrometer fitted with sodium chloride prisms. The nmr apectra were recorded with a Varian A-60 spectrometer. The mass spectra were measured with an AEI MS-9 mass spectrometer at an ionizing energy of 70 eV.
Vol. 33, No. 3, March 1968
CHLORINATION OF BENZYL CHLOROMETHYL SULFIDES1083
From p-fluorobenzyl mercaptan there was prepared the corresponding chloromethyl sulfide l l a in 76.5% yield, bp 67' (0.3 mm). The sulfide was likewise characterized as its sulfone 13a, mp 132' (from cyclohexane). Anal. Calcd for CJ[sClF02S: C, 43.15; H, 3.62; S, 14.40. Found: C,43.33; H, 3.69; S, 14.42. From m-trifluoromethylbenzyl mercaptan there was prepared the corresponding chloromethyl sulfide l l c in 79% yield, bp 67' (0.2 mm). The sulfide. was oxidized to its sulfone (13c), mp 90" (from cyclohexane), for purposes of characterization. Anal. Calcd for CqH&lF302S: C, 39.60; H, 2.97; C1, 31.04. Found: C, 39.64; H,2.96; C1,13.00. From p-nitrobenzyl mercaptanl6 there was prepared the corresponding chloromethpl sulfide 14, mp 50-51' (from CClr), in 70y0 yield. Oxidation of 14 gave the related sulfone as colorless needles from chloroform-cyclohexane, mp 149.5-150.5". Anal. Calcd for CsH8C1N04S; C, 38.48; H, 3.23; C1, 14.20. Found: C,38.28; H,3.16; C1,14.02. General Procedure far the Chlorination and Oxidation of the Benzyl Chloromethyl Sulfides.-Under a nitrogen atmosphere, a solution of 1.0 g (7.3 mmol) of sulfuryl chloride in 10 ml of carbon tetrachloride was added dropwise to a stirred solution of 1.6 g (7.3 mmol) of chloromethyl p-nitrobenzyl sulfide (14) in 15 ml of the same solvent a t 23'. After addition of the sulfuryl chloride had been completed, the solution was refluxed for 2.5 hr and cooled, and the solvent was removed under reduced pressure. The residue was immediately oxidized with 3.1 g (18.2 nimoles) of rn-chloroperbenzoic acid in cold chloroform. The usual work-up8 gave a pale yellow oil, the nmr spectrum of which was recorded. Careful chromatography of the oil on 80 g of silica gel [elution with benzene-chloroform (4: l)] afforded 15 and 16 in a ratio of 3: 2 (total weight, 1.5 g). The first compound to be eluted (15) was obtained as colorless needles from chloroform--cyclohexane, mp 106.5-107.5'. Anal. Calcd for C81I&b?;Od3: C, 33.82; H , 2.48; C1, 24.96. Found: C, 33.75; H , 2.37; C1,24.83. The minor component (16) was obtained as colorless needles from chloroform-hexane, mp 121-122'. Anal. Calcd for CgH?CLNO4S: C, 33.82; H, 2.48; C1, 24.96. Found: C, 34.02; H,2.68; (21,2439. When 14 (4.34 g, 20 mmol) was treated with 4.05 g (30 mmol) of sulfuryl chloride as above, there was isolated by chromatography on silica gel (in the order of elution) 2.35 g of 17, mp 162163' (from chloroform-hexane). Anal. Calcd for C8HeClsNOaS: C, 30.16; H, 1.90; C1, 33.38. Found: C, 30.23; H , 1.96; C1,33.34.
--
(15) u'.S. Hoffman and E:. E. Reid, J . Amer. Chem. Soc., 46,1833(1923): W.J. Horn, %bid.,48, 2603 (1021).
Further elution16 with benzene-cyclohexane (4: 1) gave 250 mg of 18, mp 110-111' (from chloroform-cyclohexane). Anal. Calcd for C8HsCl1NO4S: C , 30.16; H, 1.90; C1, 33.38. Found: C,30.38; H,2.01; C1,33.61. The final compound to be eluted, mp 106.5-107.5', was found to be 15, the substance which was eluted first in the previous experiment. Further elution of the column with solvents of increasing polarity gave no additional material. In similar fashion, reaction of 11.4 g (0.06 mol) of l l a with 8.8 g (0.065 mol) of sulfuryl chloride afforded a mixture of two sulfones. Chromatography of a weighed aliquot of the total crude product indicated the mixture to be composed of 23% 13a, mp 132', and 77% 12a, mp 62' (from cyclohexane). Anal. Calcd for C8H7C12F02S: C , 37.54; H, 2.89; S, 12.61. Found: C, 37.37; H , 2.74; S,12.47. I n like fashion, l l b afforded a mixture consisting of 13b, mp 155', and 12b, mp 90.5' (from cyclohexane), in a ratio of 4: 1. Anal. Calcd for CsH&laOzS: C, 35.12; H , 2.58; S, 11.72. Found: C, 34.75; H , 2.64; S, 11.71. When I l c was treated with sulfuryl chloride and m-chloroperbenzoic acid in the above manner, there was isolated upon careful chromatography the chloro sulfones 13c, mp 90°, and 12c, mp 70.5' (from cyclohexane), in a ratio of 2: 1. Anal. Calcd for C P H ~ C ~ F ~ O ZC,S :35.19; H, 2.30; C1, 23.09. Found: C, 35.16; H,2.32; C1,22.96. I n all cases, the ratio of isolated product were found to compare favorably with the integrated intensity ratios of the various proton absorptions in the nmr spectra of the crude oxidation mixtures.
Registry No.-lla, 15894-24-3; l l b , 1589425-4; l l c , 15894-26-5; 12a, 15894-27-6; 12b, 1589428-7; 12c, 15894-29-8; 13a, 15963-74-3; 13b, 15893-98-8; 13c, 15893-96-6; 14 sulfone, 15893-97-7; 15, 15893-99-9; 16, 15894-00-5; 17, 15894-01-6; 18, 15894-02-7; p-fluorobenzyl thiuronium bromide, 15894-03-8; p-fluorobenzyl mercaptan, 15894-04-9; m-fluorobenzyl thiuronium chloride, 15894-05-0; m-fluorobenzyl mercaptan, 1589406-1 ; dibenayl sulfone, 620-32-6; CeH6CH2SO2CHC115893-97-7; C6H6?6668-15-1 ;p-NOrC~H*CH2SOzCH2CI1 C6H&H&O2CHC12, 10038-09-2; CeH&H2S02CCla, 15894-1 1-8. (16) Clean separation of 17 and 18 was not always achieved. However, fraational recrystallixation of the mixed fractions readily yielded pure 17 and 18.
